scholarly journals Early Inflammatory Cytokine Expression in Cerebrospinal Fluid of Patients with Spontaneous Intraventricular Hemorrhage

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1123
Author(s):  
Wendy C. Ziai ◽  
Adrian R. Parry-Jones ◽  
Carol B. Thompson ◽  
Lauren H. Sansing ◽  
Michael T. Mullen ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intraventricular Hemorrhage ◽  
Inflammatory Responses ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drainage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Injury Reduction ◽  
Positive Correlations ◽  
Factor Α ◽  
Perihematomal Edema

We investigated cerebrospinal fluid (CSF) expression of inflammatory cytokines and their relationship with spontaneous intracerebral and intraventricular hemorrhage (ICH, IVH) and perihematomal edema (PHE) volumes in patients with acute IVH. Twenty-eight adults with IVH requiring external ventricular drainage for obstructive hydrocephalus had cerebrospinal fluid (CSF) collected for up to 10 days and had levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNFα), and C-C motif chemokine ligand CCL2 measured using enzyme-linked immunosorbent assay. Median [IQR] ICH and IVH volumes at baseline (T0) were 19.8 [5.8–48.8] and 14.3 [5.3–38] mL respectively. Mean levels of IL-1β, IL-6, IL-10, TNF-α, and CCL2 peaked early compared to day 9–10 (p < 0.05) and decreased across subsequent time periods. Levels of IL-1β, IL-6, IL-8, IL-10, and CCL2 had positive correlations with IVH volume at days 3–8 whereas positive correlations with ICH volume occurred earlier at day 1–2. Significant correlations were found with PHE volume for IL-6, IL-10 and CCL2 at day 1–2 and with relative PHE at days 7–8 or 9–10 for IL-1β, IL-6, IL-8, and IL-10. Time trends of CSF cytokines support experimental data suggesting association of cerebral inflammatory responses with ICH/IVH severity. Pro-inflammatory markers are potential targets for injury reduction.

scholarly journals Recirculatory Fibrinolytic-Assisted External Ventricular Drainage (EVD) for Intraventricular Hemorrhage

2021 ◽  
Author(s):  
Zhen QIN ◽  
John Ching Kwong Kwok ◽  
Peter Yat Ming Woo ◽  
Carmen Yim ◽  
Chi Hang Chon
Keyword(s):  
Intraventricular Hemorrhage ◽  
Treatment Time ◽  
Ex Vivo ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drainage ◽  
Ventricular Drainage ◽  
Fibrinolytic Agent ◽  
Recirculatory Flow ◽  
Previous Clinical Trial ◽  
Clinical Trial Results

Abstract Background Elevated intracranial pressure and acute obstructive hydrocephalus secondary to intraventricular hemorrhage (IVH) can be treated by external ventricular drainage (EVD). The treatment time and the risk of EVD-related complications can be reduced with fibrinolytic agents’ instillation via an EVD catheter, but previous clinical trial results did not reveal a significant improvement in terms of long-term functional outcomes. A recirculatory fibrinolytic-assisted EVD system was designed. The clot dissolution effectiveness of the system under different drug dosages and fluid flow rates was tested in an ex vivo model. Results The results showed that the mean clot mass was quickly reduced in an initial fibrinolytic agent dose-independent stage, followed by a dose-dependent stage. Elevating fibrinolytic agent dosages beyond a certain threshold did not contribute to shorter dissolution times. Optimal treatment parameters for such a system were determined. A recirculatory flow rate of 10–18 ml/min with a low-dose of 30 000–60 000 IU of uPA resulted in an 80% clot mass reduction within four hours. Conclusions This recirculating fibrinolytic system is a promising novel modification of conventional IVH treatment that could reduce clot dissolution times and procedure-related complications.

Abstract WMP86: Evaluation of Cerebrospinal Fluid Dynamics and External Ventricular Drain Management in the Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage trial (CLEAR III)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Wendy Ziai ◽  
Mariam Bhuiyan ◽  
Nichol McBee ◽  
Rachel Dlugash ◽  
Kevin Sheth ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intraventricular Hemorrhage ◽  
Obstructive Hydrocephalus ◽  
External Ventricular Drain ◽  
Randomized Study ◽  
Recombinant Tissue Plasminogen Activator ◽  
Clot Lysis ◽  
Csf Dynamics ◽  
Double Blind ◽  
Csf Drainage

Background: Acute obstructive hydrocephalus secondary to spontaneous intracerebral/intraventricular hemorrhage (ICH/IVH) requires early cerebrospinal fluid (CSF) drainage to reduce intracranial pressure (ICP). Extensive CSF drainage may reduce IVH clot burden. We characterize CSF dynamics, strategies and impact on end of treatment (EOT) IVH volume (72 hours post randomization [Rand]) in the CLEAR III trial. Methods: Prospective analysis of CSF output in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular recombinant tissue plasminogen activator (rtPA) vs. EVD + placebo for treatment of obstructive IVH and intracerebral hemorrhage (ICH) volume <30cc. CSF output was recorded every 4 hours until 7 days post Rand, and compared by clinical and radiological variables. Results: Daily median CSF output in the first week was 188cc (IQR: 125, 252). Maximum daily EVD drip settings were <10mmHg in 27.8%, =10 in 44.1% and >10 in 28.1%. Independent predictors of higher daily CSF output after adjustment for initial IVH volume (p=0.04) were lower drip setting (p<0.001), lower age (p<0.001), male sex (p=0.03), dual EVD (p=0.005), CSF protein (p<0.001) and ICP>20mmHg (P=0.007). Both EOT IVH volume and change in IVH volume (ChgIVH) (over 1 st week) were independently associated with total CSF output (P=0.004/<0.001, respectively), and initial IVH volume (P<0.001/<0.001)). Early opening of 3 rd and 4 th ventricle (P=0.03) was associated with lower EOT volumes, while CSF protein (P=0.02), and side of EVD ipsilateral to largest IVH (P=0.04) were associated with ChgIVH. Shunting for hydrocephalus was performed in 18.6% over 1 year follow-up and was associated with higher total CSF output over first week (P<0.001). Conclusions: CSF circulation in severe IVH can be assessed by CSF output which is associated with EVD drip management and other clinical variables. EOT IVH volume and IVH volume reduction are important surrogate endpoints which are related to CSF dynamics. VP shunt requirement in spontaneous IVH is associated with early CSF output levels. These results permit future correlation of CSF output with treatment rendered (thrombolysis versus placebo) with upcoming unblinding of the trial.

scholarly journals Markers of Inflammation and Infection in Sepsis and Disseminated Intravascular Coagulation

2019 ◽  
Vol 25 ◽  
pp. 107602961984333 ◽  
Author(s):  
Priya Patel ◽  
Amanda Walborn ◽  
Matthew Rondina ◽  
Jawed Fareed ◽  
Debra Hoppensteadt
Keyword(s):  
Disseminated Intravascular Coagulation ◽  
Severity Of Illness ◽  
Diagnostic Algorithm ◽  
Fold Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Intravascular Coagulation ◽  
Chromogenic Assay ◽  
Markers Of Inflammation ◽  
Positive Correlations ◽  
Factor Α

Sepsis is a severe systemic inflammatory response to infection that manifests with widespread inflammation as well as endothelial and coagulation dysfunction that may lead to hypotension, organ failure, shock, and death. Disseminated intravascular coagulation (DIC) is a complication of sepsis involving systemic activation of the fibrinolytic and coagulation pathways that can lead to multi-organ dysfunction, thrombosis, and bleeding, with a 2-fold increase in mortality. This study demonstrates the diagnostic and prognostic value of profiling various biomarkers of inflammation and infection in patients with sepsis-associated DIC to assess the severity of illness. Deidentified samples were obtained from adult patients with sepsis and suspected DIC. Platelet count, prothrombin time, D-dimer, and fibrinogen levels were used to assign International Society of Thrombosis and Hemostasis DIC scores to plasma samples from 103 patients with sepsis and suspected DIC. Using commercially available enzyme-linked immunosorbent assay, chromogenic assay, and RANDOX Biochip methods, levels of procalcitonin (PCT), extracellular nucleosomes, interleukin (IL) 6, IL-8, IL-10, and tumor necrosis factor α (TNFα) were measured in patients with sepsis and DIC and compared to levels in healthy individuals. Elevated levels of PCT, IL-6, IL-8, IL-10, and TNFα were observed in most patients with sepsis and DIC. Additionally, the levels of these markers show significant positive correlations with each other and with DIC score. Currently, no single biomarker can effectively diagnose DIC in patients with sepsis. This study lays the groundwork for the development of a diagnostic algorithm using several markers of inflammation and infection and DIC score as parameters in assessing severity of sepsis-associated coagulopathy in a clinical setting.

Clinical and Serological Biomarkers of Treatment’s Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade

2018 ◽  
Vol 17 (10) ◽  
pp. 780-792 ◽  
Author(s):  
Laura Iulia Bărcuţean ◽  
Andreea Romaniuc ◽  
Smaranda Maier ◽  
Zoltan Bajko ◽  
Anca Moţăţăianu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demographic Data ◽  
Active Form ◽  
Positive Influence ◽  
Serum Samples ◽  
Disability Score ◽  
Positive Correlations ◽  
Multiple Sclerosis Patients ◽  
Factor Α ◽  
Serological Biomarkers

Introduction: We evaluated the peripheral immune panel of Multiple Sclerosis (MS) patients treated for more than 10 years with interferon-beta1b (IFNβ-1b) and aimed to identify possible biomarkers of treatment response. Material and Methods: Serum samples from 70 MS patients treated with IFNβ-1b more than a decade were analysed for 15 cytokines, that were correlated with the disability score, annual relapse ratio (ARR): the total number of relapses-ARR_0, relapse on treatment-ARR_1 and demographic data. Two groups were defined based on the levels of disability, calculated using the Expanded Disability Status Scale (EDSS): G1 – recurrent-remissive and G2 – secondary-progressive. Furthermore, we split the patients based on gender (G1_f, G1_m, G2_f, G2_m). Results: The ARR was reduced after treatment was instituted. We found positive correlations between IL_25 and EDSS in G1_f and G2_f, tumor necrosis factor α (TNFα) and ARR_1 and ARR_0 in G1, and IL_17F with ARR_1. Negative correlations were for IL_25 and ARR_0 and ARR_1. SCD40L intensely positively correlated with IL_31 in G1 and G2. Conclusion: After more than a decade of treatment, IFNβ-1b offers good results by reducing relapses and slowing disability progression. Several biomarkers can be used to assess the patient’s response. High levels of IL_17 and TNFα will indicate a more active form of the disease. IL-25 may exert a positive influence in male MS patients and should be considered for future studies, together with the co-modulation between sCD40L and IL_31. Our method allowed us to screen the peripheral immune panel and can be used for assessing the peripheral levels of the above-mentioned cytokines.

scholarly journals Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3573
Author(s):  
Lian-Chun Li ◽  
Zheng-Hong Pan ◽  
De-Sheng Ning ◽  
Yu-Xia Fu
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathway ◽  
Morphological Changes ◽  
Raw264.7 Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Factor Α ◽  
Oxide Synthase ◽  
Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

scholarly journals Manipulation of Quercetin and Melatonin in the Down-Regulation of HIF-1α, HSP-70 and VEGF Pathways in Rat’s Kidneys Induced by Hypoxic Stress

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582094979
Author(s):  
Aliah R. Alshanwani ◽  
Sameerah Shaheen ◽  
Laila M. Faddah ◽  
Ahlam M. Alhusaini ◽  
Hanaa M. Ali ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Histopathological Examination ◽  
Hemoglobin Concentration ◽  
Vascular Endothelial ◽  
Hsp 70 ◽  
Reactive Protein ◽  
Defensive Role ◽  
Factor Α ◽  
Endothelial Growth Factor

Hypoxia may lead to inflammatory responses by numerous signaling pathways. This investigation intended to inspect the defensive role of Quercetin (Quer) and/ or Melatonin (Mel) against reno toxicity induced by Sodium nitrite (Sod ntr). Sod ntr injection significantly decreased blood hemoglobin concentration (Hb) with a concurrent increase in serum tumor necrosis factor- α, interleukin-6, C-reactive protein, creatinine, and urea levels. Over protein-expression of vascular endothelial growth factor and heat shock, protein-70 and mRNA of HIF-1α were also observed. Pretreatment of the Sod ntr- injected rats with the aforementioned antioxidants; either alone or together significantly improved such parameters. Histopathological examination reinforced the previous results. It was concluded that the combined administration of Quer and Mel may be useful as a potential therapy against renal injury induced by Sod ntr. HIF-1α and HSP-70 are implicated in the induction of hypoxia and its treatment.

scholarly journals Role of MDA5 in regulating CXCL10 expression induced by TLR3 signaling in human rheumatoid fibroblast-like synoviocytes

2021 ◽  
Author(s):  
Tatsuro Saruga ◽  
Tadaatsu Imaizumi ◽  
Shogo Kawaguchi ◽  
Kazuhiko Seya ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Neutralizing Antibody ◽  
Poly I:C ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Inflammatory Reactions ◽  
Polyinosinic:Polycytidylic Acid ◽  
Tlr3 Signaling ◽  
Fibroblast Like Synoviocytes

AbstractC-X-C motif chemokine 10 (CXCL10) is an inflammatory chemokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Melanoma differentiation-associated gene 5 (MDA5) is an RNA helicase that plays a role in innate immune and inflammatory reactions. The details of the regulatory mechanisms of CXCL10 production and the precise role of MDA5 in RA synovitis have not been fully elucidated. The aim of this study was to examine the role of MDA5 in regulating CXCL10 expression in cultured human rheumatoid fibroblast-like synoviocytes (RFLS). RFLS was stimulated with Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA mimetic. Expression of interferon beta (IFN-β), MDA5, and CXCL10 was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay. A neutralizing antibody of IFN-β and siRNA-mediated MDA5 knockdown were used to determine the role of these molecules in regulating CXCL10 expression downstream of TLR3 signaling in RFLS. Poly I:C induced IFN-β, MDA5, and CXCL10 expression in a concentration- and time-dependent manner. IFN-β neutralizing antibody suppressed the expression of MDA5 and CXCL10, and knockdown of MDA5 decreased a part of CXCL10 expression (p < 0.001). The TLR3/IFN-β/CXCL10 axis may play a crucial role in the inflammatory responses in RA synovium, and MDA5 may be partially involved in this axis.

scholarly journals Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1210
Author(s):  
Júlia Costa ◽  
Marta Gromicho ◽  
Ana Pronto-Laborinho ◽  
Conceição Almeida ◽  
Ricardo A. Gomes ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Motor Neurons ◽  
Neurological Diseases ◽  
Disease Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Progression Rate ◽  
Therapeutic Trials ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

scholarly journals Early Confirmation of Mycoplasma pneumoniae Infection by Two Short-Term Serologic IgM Examination

Diagnostics ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 353
Author(s):  
Ha Eun Jeon ◽  
Hyun Mi Kang ◽  
Eun Ae Yang ◽  
Hye Young Han ◽  
Seung Beom Han ◽  
...  
Keyword(s):  
Mycoplasma Pneumoniae ◽  
Early Stage ◽  
Immunoglobulin M ◽  
Enzyme Linked Immunosorbent Assay ◽  
Short Term ◽  
Serologic Tests ◽  
Polymerase Chain ◽  
Positive Correlations ◽  
Patient Selection Bias ◽  
Mycoplasma Pneumoniae Infection

The aim of the present study is to re-evaluate the clinical application of two-times serologic immunoglobulin M (IgM) tests using microparticle agglutination assay (MAA), an enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) assay in diagnosing Mycoplasma pneumoniae (MP) infection. A retrospective analysis of 62 children with MP pneumonia during a recent epidemic (2019–2020) was conducted. The MAA and ELISA immunoglobulin M (IgM) and IgG measurements were conducted twice at admission and around discharge, and MP PCR once at presentation. Diagnostic rates in each test were calculated at presentation and at discharge. The seroconverters were 39% (24/62) of patients tested by MAA and 29% (18/62) by ELISA. At presentation, the diagnostic positive rates of MAA, ELISA, and PCR tests were 61%, 71%, and 52%, respectively. After the second examination, the rates were 100% in both serologic tests. There were positive correlations between the titers of MAA and the IgM values of ELISA. The single serologic IgM or PCR tests had limitations to select patients infected with MP in the early stage. The short-term, paired IgM serologic tests during hospitalization can reduce patient-selection bias in MP infection studies.

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